Besides, nAChRs-based therapies have been used in combination with chemotherapy drugs to reduce the side effects. This strategy requires lower doses of chemotherapy drugs compared to the conditions that must be used alone. Here, we discussed the experimental and clinical studies that show the nAChRs involvement in response to chemotherapy agents. Also, controversies relating to the effects of nAChR on chemotherapy-induced apoptosis are in our focus in this review article. Delineating the complex influences of nAChRs would be of great interest in establishing new effective chemotherapy regimens.Rehmanniae Radix Preparata (RR) and Corni Fructus (CF) are commonly used together for the treatment of chronic kidney disease (CKD) in the clinical practices for thousands of years. However, little information on their synergy mechanism is available.
In this study, an integrated approach combining ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabonomics and network pharmacology was adopted to elucidate the cooperation mechanism of RR and CF on the amelioration of CKD. Furthermore, the targets from network pharmacology and metabolism pathways were jointly analyzed. Finally, the activities of key metabolic enzymes were experimentally validated by ELISA.
Metabolic profiling indicated that the metabolic disturbance in plasma was markedly alleviated after treatment. Nine putative biomarkers mainly involving in phenylalanine, tyrosine and tryptophan biosynthesis and tyrosine metabolism were identified. Moreover, the compound-target-pathway network of RR and CF for CKD treatment was constructed by network pharmacology, which was related to tyrosine metabolism and arginine and proline metabolism. The results were partly consistent with the findings of plasma metabolomics.
In conclusion, this study solidly supported and enhanced current understanding of the synergy effects of RR and CF on CKD. Meanwhile, it also confirmed the feasibility of combining metabolomics and network pharmacology to identify active components and elucidate the pharmacological effects of traditional Chinese medicines (TCMs).
In conclusion, this study solidly supported and enhanced current understanding of the synergy effects of RR and CF on CKD. https://www.selleckchem.com/products/py-60.html Meanwhile, it also confirmed the feasibility of combining metabolomics and network pharmacology to identify active components and elucidate the pharmacological effects of traditional Chinese medicines (TCMs).The aim of our study was to clarify the cardioprotection of chronic intermittent hypobaric hypoxia (CIHH) and the underlying mechanism in spontaneously hypertensive rats (SHR).
Adult male rats were divided into normal blood pressure Wistar-Kyoto rats (WKY) control (WKY-CON), WKY rats with CIHH treatment (WKY-CIHH), SHR control (SHR-CON) and SHR with CIHH treatment (SHR-CIHH) groups. SHR-CIHH and WKY-CIHH rats were subjected to hypobaric hypoxia simulating 4000-m altitude for 35days, 5h per day. Arterial blood pressure and cardiac function parameters, including ejection fraction, fractional shortening and left ventricular (LV) wall thickness, were evaluated. Cardiac pathomorphology and myocardial fibrosis were determined. The expression of angiotensin-converting enzyme (ACE), ACE2, Ang II, Ang1-7, AT1 receptor, Mas receptor, IL-6, TNF-α，IL-10, SOD and MDA were assayed in myocardium.
CIHH significantly decreased arterial blood pressure, alleviated LV hypertrophy, and improved cardiovascular function in SHR (P&lt;0.05-0.01). Also, CIHH protected SHR heart against morphological changes and fibrosis. In addition, CIHH significantly down-regulated the ACE/Ang II/AT1 receptor axis and up-regulated the ACE2/Ang1-7/Mas axis of renin-angiotensin system (RAS) in SHR (P&lt;0.05-0.01). CIHH significantly reduced IL-6, TNF-α, and MDA levels, but increased IL-10 and SOD in SHR myocardium (P&lt;0.05-0.01).
The CIHH treatment protected the heart of SHR against LV remodelling and myocardial fibrosis, which might be carried out through a balance in the ACE/Ang II/AT1 axis and the ACE2/Ang1-7/Mas axis of the RAS to reduce inflammation, and inhibit oxidative stress.
The CIHH treatment protected the heart of SHR against LV remodelling and myocardial fibrosis, which might be carried out through a balance in the ACE/Ang II/AT1 axis and the ACE2/Ang1-7/Mas axis of the RAS to reduce inflammation, and inhibit oxidative stress.In vitro and in vivo studies suggest that the mu-opioid receptor (MOR) is involved in tumorigenesis, and metastasis in cancer. In humans, the use of MOR agonists (opioids) is associated with head and neck squamous cell carcinoma (HNSCC) progression. In the present study, we aimed to examine the role of MOR activation in MOR (+) HNSCC.
FaDu, MDA686Tu and UMSCC47 cell lines were used in in vitro and in vivo experiments. Cells and animals were treated with a highly selective MOR agonist DAMGO, [D-Ala (2), Me Phe (4), Glycol (5)]-enkephalin] or saline 0.9%.
MOR activation significantly increased the proliferation, colony formation, invasion, and migration of FaDu and MDA6868Tu cells and promoted tumor growth in vivo.
These findings suggest that MOR is implicated in tumorigenesis of HNSCC. Overall, our findings identify that MOR could be used as a potential therapeutic target in patients with MOR (+) HNSCC.
These findings suggest that MOR is implicated in tumorigenesis of HNSCC. Overall, our findings identify that MOR could be used as a potential therapeutic target in patients with MOR (+) HNSCC.Vitamin D plays an important role in the regulation of ovulatory dysfunction. We aimed to study the effect of vitamin D on letrozole-induced PCOS in female rats.
40 non-pregnant Wistar rats were divided into four groups group I control (received 1?ml of 1% aqueous solution of (CMC)/d orally), group II letrozole-induced PCOS group (received letrozole 200?μg/d orally), group III vitamin D-treated group (received vitamin D 1000?IU/kg/day), group IV letrozole and vitamin D treated group (received letrozole and vitamin D as group II and group III for 90?days). BMI, ovarian weight, serum vitamin D, biochemical metabolic and oxidative stress markers were evaluated, ovarian tissues glutathione, malondialdehyde levels and caspase-3 activity were measured. Histopathological examination of the ovary and coronary artery were done.
Letrozole-induced typical PCOS with significant decrease in vitamin D and coronary vasculopathy. Group II shows insignificant change in all parameters but there is significant increase in vitamin D and decrease in triglyceride and glutathione.